Development of pathogenesis-based therapy for polyglutamine diseases

• Project/Area Number: 17025020
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: SOBUE Gen Nagoya University, 大学院・医学系研究科, 教授 (20148315)
• Co-Investigator(Kenkyū-buntansha): TANAKA Fumiaki 名古屋大学, 大学院・医学系研究科, 准教授 (30378012) ; KATSUNO Masahisa 名古屋大学, 高等研究院, 特任講師 (50402566) ; 服部 直樹 名古屋大学, 医学部・附属病院, 准教授 (10402570) ; 道勇 学 愛知医科大学, 医学部, 教授 (90293703)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥167,100,000 (Direct Cost: ¥167,100,000); Fiscal Year 2009: ¥33,400,000 (Direct Cost: ¥33,400,000); Fiscal Year 2008: ¥33,000,000 (Direct Cost: ¥33,000,000); Fiscal Year 2007: ¥34,000,000 (Direct Cost: ¥34,000,000); Fiscal Year 2006: ¥34,000,000 (Direct Cost: ¥34,000,000); Fiscal Year 2005: ¥32,700,000 (Direct Cost: ¥32,700,000)
• Keywords: ポリグルタミン / 球脊髄性筋萎縮症(SBMA) / 脊髄小脳失調症(SCA) / 転写障害 / TGF-β / 球脊髄性筋萎縮症 / 運動ニューロン / ユビキチン / プロテアソーム / 17-DMAG / ポリグルタミン病 / CHIP / 軸索輸送 / モーター蛋白質 / dnactin1 / ニューロフィラメント / HSP / 17-AAG / GGA / ユビキチン-プロテアソーム

Research Abstract

In this study, we demonstrated that the disruption of TGF-β signaling by the pathogenic androgen receptor (AR) is associated with polyglutamine-induced motor neuron damage in SBMA. Our in vivo analyses also showed that Hsp90 inhibitors facilitate proteasomal degradation of the pathogenic AR. These results indicate that pharmacological modification of UPS activity and cellular signals such as TGF-β appear to be promising therapeutic approaches for SBMA and other polyglutamine diseases.

Research Products

• [Journal Article] Disrupted TGF-beta signaling in spinal and bulbar muscular atrophy (2010)
  • Author(s): Katsuno, M., Adachi, H., Minamiyama, M., Waza, M., Doi, H., Kondo, N., Mizoguchi, H., Nitta, A., Yamada, K., Banno, H., Suzuki, K., Tanaka, F., Sobue, G.
  • Journal Title: J. Neurosci 30 Pages: 5702-5712
  • Peer Reviewed
• [Journal Article] The profile of motor unit number estimation (MUNE) in spinal and bulbar Museular atrophy. (2010)
  • Author(s): Suzuki K, Katsuno M, Banno H, Takeuchi Y, Kawashima M, Suga N, Hashizume A, Hama T, Uchida K, Yamashita F, Nakamura T, Hirayama M, Tanaka F, Sobue G.
  • Journal Title: J Neurol Neurosurg Psychiatry 81 Pages: 567-571
  • Peer Reviewed
• [Journal Article] Disrupted TGF-beta signaling in spinal and bulbar muscular atrophy. (2010)
  • Author(s): Katsuno M, Adachi H, Minamiyama M, Waza M, Doi H, Kondo N, Mizoguchi H, Nitta A, Yamada K, Banno H, Suzuki K, Tanaka F, Sobue G.
  • Journal Title: J Neurosci. 30 Pages: 5702-5712
  • Peer Reviewed
• [Journal Article] Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis. (2010)
  • Author(s): Sone J, Niwa JI, Kawai K, Ishigaki S, Yamada SI, Adachi H, Katsuno M, Tanaka F, Doyu M, Sobue G.
  • Journal Title: J Neurosci Res. 88 Pages: 123-135
  • Peer Reviewed
• [Journal Article] Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy (2009)
  • Author(s): Palazzolo, I., Stack, C., Kong, L., Musaro, A., Adachi, H., Katsuno, M., Sobue, G., Taylor, J.P., Sumner, C.J., Fischbeck, K.H., Pennuto, M.
  • Journal Title: Neuron 63 Pages: 316-328
  • Peer Reviewed
• [Journal Article] Getting a handle on Huntington's disease, the case for cholesterol (2009)
  • Author(s): Katsuno, M., Adachi, H., Sobue, G.
  • Journal Title: Nat. Med. 15 Pages: 253-254
  • Peer Reviewed
• [Journal Article] TDP-43 Depletion Induces Neuronal Cell Damage through Dysregulation of Rho Family GTPases (2009)
  • Author(s): Iguchi, Y., Katsuno, M., Niwa, J., Yamada, S., Sone, J., Waza, M., Adachi, H., Tanaka, F., Nagata, K., Arimura, N., Watanabe, T., Kaibuchi, K., Sobue, G.
  • Journal Title: J Biol Chem. 284 Pages: 22059-22066
  • Peer Reviewed
• [Journal Article] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy (2009)
  • Author(s): Banno, H., Katsuno, M., Suzuki, K., Takeuchi, Y., Kawashima, M., Suga, N., Takamori, M., Ito, M., Nakamura, T., Matsuo, K., Yamada, S., Oki, Y., Adachi, H., Minamiyama, M., Waza, M., Atsuta, N., Watanabe, H., Fujimoto, Y., Nakashima, T., Tanaka, F., Doyu, M., Sobue, G.
  • Journal Title: Ann Neurol 65 Pages: 140-150
  • Peer Reviewed
• [Journal Article] 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in a SBMA model mouse (2009)
  • Author(s): Tokui, K., Adachi, H., Waza, M., Katsuno, M., Minamiyama, M., Doi, H., Tanaka, K., Hamazaki, J., Murata, S., Tanaka, F., Sobue, G.
  • Journal Title: Hum. Mol. Genet. 18 Pages: 898-910
  • Peer Reviewed
• [Journal Article] Heat shock proteins in neurodegenerative diseases : Pathogenic roles and therapeutic implications. (2009)
  • Author(s): Adachi H, Katsuno M, Waza M, Minamiyama M, Tanaka F, Sobue G.
  • Journal Title: Int J Hyperthermia 25 Pages: 647-654
• [Journal Article] Correlation between pyramidal tract degeneration and widespread white matter involvement in amyotrophic lateral sclerosis : a study with tractography and diffusion-tensor imaging. (2009)
  • Author(s): Senda J, Ito M, Watanabe H, Atsuta N, Kawai Y, Katsuno M, Tanaka F, Naganawa S, Fukatsu H, Sobue G.
  • Journal Title: Amyotroph Lateral Scler. 10 Pages: 288-294
  • Peer Reviewed
• [Journal Article] Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. (2009)
  • Author(s): Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH, Pennuto M.
  • Journal Title: Neuron 63 Pages: 316-328
  • Peer Reviewed
• [Journal Article] TDP-43 Depletion Induces Neuronal Cell Damage through Dysregulation of Rho Family GTPases. (2009)
  • Author(s): Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G.
  • Journal Title: J Biol Chem. 284 Pages: 22059-22066
  • Peer Reviewed
• [Journal Article] Pathogenesis-targeting Therapeutics for Spinal and Bulbar Muscular Atrophy (SBMA) (2009)
  • Author(s): Suzuki K, et.al.
  • Journal Title: Neuropathology (in press)
  • Peer Reviewed
• [Journal Article] Neuropathology and therapeutic intervention in spinal and bulbar muscular atrophy (2009)
  • Author(s): Benno H, et.al.
  • Journal Title: Int. J. Mel. Sc (in press)
  • Peer Reviewed
• [Journal Article] Correlation between pyramidal tract degeneration and wide spread white matter involvement in amyotrophic lateral sclerosis : A study with tractography and diffusion-tensor imaging (2009)
  • Author(s): Senda J., et.al.
  • Journal Title: Aolyotroph. Lateral Soler (in press)
  • Peer Reviewed
• [Journal Article] Getting a handle on Huntington's disease : the case for cholesterol (2009)
  • Author(s): Katsuno M, et.al.
  • Journal Title: Nat. Med 15 Pages: 253-254
  • Peer Reviewed
• [Journal Article] Poryglutamine-expanded androgen receptor truncation fragments activate a Bak-dependent apoptotic cascade mediated by DP 5/Hrk (2009)
  • Author(s): Young JE, et.al.
  • Journal Title: J. Neurosci 29 Pages: 1987-1997
  • Peer Reviewed
• [Journal Article] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy (2009)
  • Author(s): banno H, et.al.
  • Journal Title: Ann. Neural 65 Pages: 140-150
  • Peer Reviewed
• [Journal Article] 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in a SBMA model mouse (2009)
  • Author(s): Tokui K, et.al.
  • Journal Title: Mum. Mol. Genet 18 Pages: 898-910
  • Peer Reviewed
• [Journal Article] CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA (2008)
  • Author(s): Suzuki, K., Katsuno, M., Banno, H., Takeuchi, Y., Atsuta, N., Ito, M., Watanabe, H., Yamashita, F., Hori, N., Nakamura, T., Hirayama, M., Tanaka, F., Sobue, G.
  • Journal Title: Brain 131 Pages: 229-239
  • Peer Reviewed
• [Journal Article] Walking capacity evaluated by the 6-minute walk test in Spinal and bulbar muscular atrophy (2008)
  • Author(s): Takeuchi Y, et.al.
  • Journal Title: Muscle Nerve 38 Pages: 964-971
  • Peer Reviewed
• [Journal Article] Molecular Genetics and Biomarkers of Polyglutamine Diseases (2008)
  • Author(s): Katsuno M, et.al.
  • Journal Title: Current Mol. Med 8 Pages: 221-234
  • Peer Reviewed
• [Journal Article] Cognitive jmpairment in spinocerebellar ataxia type 6 (2008)
  • Author(s): Suenaga M, et.al.
  • Journal Title: J. Neurol. Neurosurg : Psychiatry 79 Pages: 496-499
  • Peer Reviewed
• [Journal Article] CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA (2008)
  • Author(s): Suzuki K, et.al.
  • Journal Title: Brain 131 Pages: 229-239
  • Peer Reviewed
• [Journal Article] CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA (2008)
  • Author(s): Suzuki K, Katsuno M, Banno H, Takeuchi Y, Atsuta N, Ito M, Watanabe H, Yamashita F, Hori N, Nakamura T, Hirayama M, Tanaka F, Sobue G
  • Journal Title: Brain 131 Pages: 229-239
  • Peer Reviewed
• [Journal Article] CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model (2007)
  • Author(s): Adachi, H., Waza, M., Tokui, K., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., Sobue, G.
  • Journal Title: J. Neurosci 27 Pages: 5115-5126
  • Peer Reviewed
• [Journal Article] ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor (2007)
  • Author(s): Yang, Z., Chang, Y.J., Yu, I.C., Yeh, S., Wu, C.C., Miyamoto, H., Merry, D.E., Sobue, G., Chen, L.M, Chang, S.S.& Chang, C
  • Journal Title: Nat. Med 13 Pages: 348-353
  • Peer Reviewed
• [Journal Article] Altered venous capacitance as a cause of postprandial hypotension in multiple system atrophy (2007)
  • Author(s): Takamori M, Hirayama M, Kobayashi R, Ito H, Mabuchi N, Nakamura T, Hori N, Koike Y, Sobue G
  • Journal Title: Clin Auton Res 17 Pages: 20-25
  • Peer Reviewed
• [Journal Article] Reduces Mutant Androgen Receptor protein and Ameliorates Phenotypes of the Spinal and Bulbar Muscular Atrophy Transgenic Mouse Model (2007)
  • Author(s): Adachi H, Waza M, Tokui K, Katsuno M, Minamiyama M, Tanak F, Doyu M, Sobue G
  • Journal Title: J Neurosci 27 Pages: 5115-5126
  • Peer Reviewed
• [Journal Article] Congenial fibrosis of the extraocular muscles (CFEOM) sydrome associated with progressive cerebellar ataxia (2007)
  • Author(s): Yoshida K, Okano T, Hoshi K, Yahikozawa H, Suzuki K, Bannno H, Tamura T, Sobue G, Ikeda S
  • Journal Title: AM J Med Genet 143A Pages: 1494-1501
  • Peer Reviewed
• [Journal Article] Enhanced aquaporin-4 immunoreactivity in sporadic Creutzfeldt-Jakob disease (2007)
  • Author(s): Iwasaki Y, Mimuro M, Yoshida M. Hashizume Y, Ito M, Kitamoto T, Wakayama Y, Sobue G
  • Journal Title: Neuropathology 27 Pages: 314-323
  • NAID: 10021235965
  • Peer Reviewed
• [Journal Article] Widespread spinal cord invovement in progressive supranuclear palsy (2007)
  • Author(s): Iwasaki Y, Yoshida M. Hashizume Y, Hattori M, Aiba I, Sobue G
  • Journal Title: Neuropathology 27 Pages: 331-340
  • Peer Reviewed
• [Journal Article] Gene expressions specifically detected in motor neurons (dynactin 1, early growth response 3, Acetyl-CoA transporter, death receptor 5, and cyclin C) differentially correlate to athologic markers in sporadic amyotrophic lateral sclerosis (2007)
  • Author(s): Jiang Y, Yamamoto M, Tanaka F, Ishigaki S, Katsuno M, Adachi H, Niwia J, Doyu M, Yoshida M, Hashizume Y, Sobue G
  • Journal Title: Neuropathol Exp Neurol 66 Pages: 617-627
  • Peer Reviewed
• [Journal Article] Ataxic vs painful form of paraneoplastic neuropathy (2007)
  • Author(s): Oki Y, Koike H, Iijima M, Mori K, Hattori N, Katsuno M, Nakamura T, Hirayama M, Tanaka F, Shiraishi M, Yazaki S, Nokura K, Yamamoto H, Sobue G
  • Journal Title: Neurology 69 Pages: 564-572
  • Peer Reviewed
• [Journal Article] Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis (2007)
  • Author(s): Tanaka K, Namba T, Arai Y, Fujimoto M, Adachi H, Sobue G, Takeuchi K, Nakai A, Mizushima T
  • Journal Title: J Biol Chem 282 Pages: 23240-23252
  • Peer Reviewed
• [Journal Article] Disulfide bond mediates aggregation, toxicity, and ubiquitylation of familial amyotrophic lateral sclerosis-linked mutant SOD1 (2007)
  • Author(s): Niwa J, Yamada S, Ishigaki S, Sone J, Takahashi M, Katsuno M, Tanaka F, Doyu M, Sobue G
  • Journal Title: J Biol Chem 282 Pages: 28087-28095
  • Peer Reviewed
• [Journal Article] Recent progress in alcoholic and thiamine-deficiency neuropathy (2007)
  • Author(s): Koike H, Oki Y, Iijima M, katsuno M, Hattori N, Sobue G
  • Journal Title: Current trend in Neurology 2 Pages: 79-85
  • Peer Reviewed
• [Journal Article] Therapeutic strategies for spinal and bulbar musculara atrophy (SBMA) (2007)
  • Author(s): Katsuno M, Bannno H, Suzuki K, Takeuchi Y, Minamiyama M, Waza M, Adachi H, Tanaka F, Sobue G
  • Journal Title: Drugns of the Future 32 Pages: 907-917
  • Peer Reviewed
• [Journal Article] Nonmyelinating Schwann cell involvement with well-preserved unmyelinated axons in Charco-Matie-Tooth disease type 1A (2007)
  • Author(s): Koike H, Iijima M, Mori K, Yamamoto M, Hattori N, Katsuno M, Tanaka F, Watanabe H, Doyu M, Yoshikawa H, Sobue G
  • Journal Title: J Neuropathol Exp Neurol 66 Pages: 1027-1036
  • Peer Reviewed
• [Journal Article] Dobutamine stress test unmasks cardiac sympathetic denervation in Parkinson's disease (2007)
  • Author(s): Nakamura T, Hirayama M, Ito H, Takamori M, Hamada K, Takeuchi S, Watanabe H, Koike Y, Sobue G
  • Journal Title: J Neurol Sci 263 Pages: 133-138
  • Peer Reviewed
• [Journal Article] Pyramidal tract degeneration in sporadic Creutzfeldt-Jakob disease (2007)
  • Author(s): Iwasaki Y, Yoshida M, Hashizume Y, Kitamoto T, Sobue G
  • Journal Title: Neuropathology 27 Pages: 434-441
  • NAID: 10021236410
  • Peer Reviewed
• [Journal Article] Hypophosphataemic neuropathy in a patient who received intravenous hyperalimentation (2007)
  • Author(s): Iguchi Y, Mori K, Koike H, Mano K, Goto Y, Kato T, Nakano T, Furukawa D, Sobue G
  • Journal Title: Neurol Neurosurg Psychiatry 78 Pages: 1159-1160
  • Peer Reviewed
• [Journal Article] In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5'splice sites (2007)
  • Author(s): Sahashi K, Masuda A, Matsuura T, Shinmi J, Zhang Z, Takeshima Y, Matsuo M, Sobue G, Ohno K
  • Journal Title: Nucleic Acids Res 35 Pages: 5995-6003
  • Peer Reviewed
• [Journal Article] Intravenous immunoglobulin therapy markedly ameliorates muscle weakness and severe pain in proximal diabetic neuropathy (2007)
  • Author(s): Kawagashira Y, Watanabe H, Oki Y, Iijima M, Koike H, Hattori N, Katsuno M, Tanaka F, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry 78 Pages: 899-901
  • Peer Reviewed
• [Journal Article] Scientific highlights. 17th International Symposium on ALS/MND Yokohama, Japan, November 30, 2006 through December 2, 2006 (2007)
  • Author(s): Sobue G
  • Journal Title: Amyotroph Lateral Scler 2 Pages: 121-123
  • Peer Reviewed
• [Journal Article] Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy (2007)
  • Author(s): Adachi H, Waza M, Katsuno M, Tanaka F, Doyu M, Sobue G
  • Journal Title: Neuropathol Appl Neurobiol 33 Pages: 135-151
  • Peer Reviewed
• [Journal Article] Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy (2007)
  • Author(s): Ito M, Watanabe H, Kawai Y, Atsuta N, Tanaka F, Naganawa S, Fukatsu H, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry 78 Pages: 722-728
  • Peer Reviewed
• [Journal Article] ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor (2007)
  • Author(s): Yang Z, Chang YJ, Yu IC, Yeh S, Wu CC, Miyamoto H, Merry DE, Sobue G, Chen LM, Chang SS, Chang C
  • Journal Title: Nat Med 13 Pages: 348-353
  • Peer Reviewed
• [Journal Article] Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SODI proteins and reduce their cellular toxicity (2007)
  • Author(s): Ishigaki S, Niwa J, Yamada S, Takahashi M, Ito T, Sone J, Doyu M, Urano F, Sobue G
  • Journal Title: Neurobiol Dis 25 Pages: 331-241
  • Peer Reviewed
• [Journal Article] Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity (2007)
  • Author(s): Ishigaki S, Niwa J, Yamada S, Takahashi M, Ito T, Sone J, Doyu M, Urano F, Sobue G
  • Journal Title: Neurobiol of Dis 25 Pages: 331-341
• [Journal Article] Gene expression profiling toward understanding of ALS pathogenesis (2006)
  • Author(s): Tanaka F, Niwa J, Ishigaki S, Katsuno M, Waza M, Yamamoto M, Doyu M, Sobue G
  • Journal Title: Ann N Y Acad Sci 1086 Pages: 1-10
• [Journal Article] Alleviating neurodegeneration by an anticancer agent : an Hsp90 inhibitor (17-AAG) (2006)
  • Author(s): Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Sobue G
  • Journal Title: Ann N Y Acad Sci 1086 Pages: 21-34
• [Journal Article] Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration (2006)
  • Author(s): Katsuno M, Adachi H, Minamiyama M, Waza M, Tokui K, Banno H, Suzuki K, Onoda Y, Tanaka F, Doyu M, Sobue G
  • Journal Title: J Neurosci 26 Pages: 12106-12117
• [Journal Article] Calcium sensing receptor ubiquitination and degradation mediated by the E3 uboquitin ligase dorfin (2006)
  • Author(s): Huang Y, Niwa J, Sobue G, Breitwieser GE
  • Journal Title: J Biol Chem 281 Pages: 11610-11617
• [Journal Article] Underediting of GlluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, dose not occur in motor neurons in ALS1 or SBMA (2006)
  • Author(s): Kawahara Y, Sun H, Ito K, Hideyama T, Aoki M, Sobue G, Tsuji S, Kwak S
  • Journal Title: Neurosci Res 54 Pages: 11-14
• [Journal Article] Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin : A pathogenic marker (2006)
  • Author(s): Banno H, Adachi H, Katsuno M, Suzuki K, Atsuta N, Watanabe H, Tanaka F, Doyu M, Sobue G
  • Journal Title: Ann Neurol 59 Pages: 520-526
• [Journal Article] Natural history of spinal and bulbar muscular atrophy (SBMA) : A study of 223 Japanes patients (2006)
  • Author(s): Atsuta N, Watanabe H, Ito M, Banno H, Suzuki K, Katsuno M, Tanaka F, Tamakoshi A, Sobue G
  • Journal Title: Brain 129 Pages: 1446-1455
• [Journal Article] Pathogenesis, animal models and therapeutics in Spinal and bulbar muscular atrophy (SBMA) (2006)
  • Author(s): Katsuno M, Adachi H, Waza M, Banno H, Suzuki K, Tanaka F, Doyu M, Sobue G
  • Journal Title: Exp Neurol 200 Pages: 8-18
• [Journal Article] Modulation of Hsp90 function in neurodegenerative disorders : a molecular-targeted therapy against disease-causing protein (2006)
  • Author(s): Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Doyu M, Sobue G
  • Journal Title: J Mol Med 84 Pages: 635-646
• [Journal Article] Archaeal proteasomes effectively degrade aggregation-prone proteins and reduce cellular toxicities in mammalian cells (2006)
  • Author(s): Yamada S, Niwa J, Ishigaki S, Takahashi M, Ito T, Sone J, Doyu M, Sobue G
  • Journal Title: J Biol Chem 281 Pages: 23842-23851
• [Journal Article] Modulation of Hsp90 function in neurodegenerative disorders : a molecular targeted therapy against disease-causing protein. (2006)
  • Author(s): Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Doyu M, Sobue G
  • Journal Title: J Mol Med (in press)
• [Journal Article] Pathogenesis, animal models and therapeutics in spinal and bulbar muscular atrophy (SBMA). (2006)
  • Author(s): Katsuno M, Adachi H, Waza M, Banno H, Suzuki K, Tanaka F, Doyu M, Sobue G
  • Journal Title: Exp Neurol (in press)
• [Journal Article] Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin : A pathogenic marker. (2006)
  • Author(s): Banno H, Adachi H, Katsuno M, Suzuki K, Atsuta N, Watanabe H, Tanaka F, Doyu M, Sobue G
  • Journal Title: Ann Neurol 59 Pages: 520-526
• [Journal Article] Disease progression of human SOD1 (G93A) transgenic ALS model rats. (2006)
  • Author(s): Matsumoto A, Okada Y, Nakamichi M, Nakamura M, Toyama Y, Sobue G, Nagai M, Aoki M, Itoyama Y, Okano H
  • Journal Title: J Neurosci Res 83 Pages: 119-133
• [Journal Article] Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA. (2006)
  • Author(s): Kawahara Y, Sun H, Ito K, Hideyama T, Aoki M, Sobue G, Tsuji S, Kwak S
  • Journal Title: Neurosci Res 54 Pages: 11-14
  • NAID: 10020613977
• [Journal Article] Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease (2005)
  • Author(s): Katsuno, M., Sang, C., Adachi, H., Minamiyama, M., Waza, M., Tanaka, F., Doyu, M., Sobue, G.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 102 Pages: 16801-16806
  • Peer Reviewed
• [Journal Article] 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration (2005)
  • Author(s): Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., Sobue, G.
  • Journal Title: Nat. Med. 11 Pages: 1088-1095
  • Peer Reviewed
• [Journal Article] Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. (2005)
  • Author(s): Katsuno M, Sang C, Adachi H, Minamiyama M, Waza M, Tanaka F, Doyu M, Sobue G
  • Journal Title: Proc Natl Acad Sci USA 102 Pages: 16801-16806
• [Journal Article] 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. (2005)
  • Author(s): Waza M, Adachi H, Katsuno M, Minamiyama M, Sang C, Tanaka F, Inukai A, Doyu M, Sobue G
  • Journal Title: Nature Med 11 Pages: 1088-1095
• [Journal Article] Gene expression profile of motor neurons in sporadic amyotrophic lateral sclerosis. (2005)
  • Author(s): Jiang YM, Yamamoto M, Kobayashi Y, Yoshihara T, Liang Y, Terao S, Takeuchi H, Ishigaki S, Katsuno M, Adachi H, Niwa J, Tanaka F, Doyu M, Yoshida M, Hashizume Y, Sobue G
  • Journal Title: Ann Neurol 57 Pages: 236-251
• [Journal Article] Widespread nuclear and cytoplasmic mutant androgen receptor accumulation in spinal and bulbar muscular atrophy. (2005)
  • Author(s): Adachi H, Katsuno M, Minamiyama M, Waza M, Sang C, Nakagomi Y, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Yoshida M, Hashizume Y, Sobue G
  • Journal Title: Brain 128 Pages: 659-670
• [Journal Article] Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy. (2005)
  • Author(s): Sone J, Hishikawa N, Koike H, Hattori N, Hirayama M, Nagamatsu M, Yamamoto M, Tanaka F, Yoshida M, Hashizume Y, Imamura H, Yamada E, Sobue G
  • Journal Title: Neurology 65 Pages: 1538-1543
• [Journal Article] The wide spectrum of clinical manifestations in Sjogren's syndrome-associated neuropathy. (2005)
  • Author(s): Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, Katsuno M, Fujita A, Aiba I, Ogata A, Saito T, Asakura K, Yoshida M, Hirayama M, Sobue G
  • Journal Title: Brain 128 Pages: 2158-2534
• [Journal Article] Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. (2005)
  • Author(s): Iijima M, Yamamoto M, Hirayama M, Tanaka F, Katsuno M, Mori K, Koike H, Hattori N, Arimura K, Nakagawa M, Yoshikawa H, Hayasaka K, Onodera O, Baba M, Yasuda H, Saito T, Nakazato M, Nakashima K, Kira J, Kaji R, Oka N, Sobue G
  • Journal Title: Neurology 64 Pages: 1471-1475
• [Journal Article] Thiamine-deficiency neuropathy in Japan. (2005)
  • Author(s): Koike H, Iijima M, Mori K, Hattori N, Sobue G
  • Journal Title: Res Adv in Neurology 2 Pages: 45-55
• [Presentation] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases. (2009)
  • Author(s): Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-17
• [Presentation] 球脊髄性筋萎縮症に対する分子治療 (2009)
  • Author(s): 勝野雅央
  • Organizer: 第50回日本神経学会総会シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. (2009)
  • Author(s): Banno H, Katsuno M, Suzuki K, Takeuchi Y, Kawashima M, Suga N, Takamori M, Ito M, Nakamura T, Matsuo K, Yamada S, Oki Y, Adachi H, Minamiyama M, Waza M, Atsuta N, Watanabe H, Fujimoto Y, Nakashima T, Tanaka F, Doyu M, Sobue G.
  • Organizer: 61th American Academy of Neurology Annual Meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 2009-04-26
• [Presentation] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases (2009)
  • Author(s): Iguchi, Y., Katsuno, M., Niwa, J., Yamada, S., Sone, J., Waza, M., Adachi, H., Tanaka, F., Nagata, K., Arimura, N., Watanabe, T., Kaibuchi, K., Sobue G.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Chicago, USA
• [Presentation] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy (2009)
  • Author(s): Banno, H., Katsuno, M., Suzuki, K., Takeuchi, Y., Kawashima, M., Suga, N., Takamori, M., Ito, M., Nakamura, T., Matsuo, K., Yamada, S., Oki, Y., Adachi, H., Minamiyama, M., Waza, M., Atsuta, N., Watanabe, H., Fujimoto, Y., Nakashima, T., Tanaka, F., Doyu, M., Sobue, G.
  • Organizer: 61th American Academy of Neurology Annual Meeting
  • Place of Presentation: Seattle, USA
• [Presentation] 神経変性疾患の病態に基づく治療開発 (2008)
  • Author(s): 祖父江元
  • Organizer: 第四回神経内科の基礎と臨床
  • Place of Presentation: 京都
  • Year and Date: 2008-11-21
• [Presentation] 分子シャペロンによる神経変性疾患の治療への展望 (2008)
  • Author(s): 祖父江元
  • Organizer: 日本ハイパーサーミア学会第25回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-09-12
• [Presentation] 神経変性疾患の病態抑止治療 (2008)
  • Author(s): 祖父江元
  • Organizer: 第39回日本内科学会北海道支部生涯教育講演会
  • Place of Presentation: 北海道
  • Year and Date: 2008-06-16
• [Presentation] 神経変性疾患の分子標的治療 : 球脊髄性筋萎縮症を中心に (2008)
  • Author(s): 祖父江元
  • Organizer: 第49回日本神経病理学会総会学術集会シンポジウムI 「末梢神経・筋疾患の臨床病理-病因解明と治療開発にはたす新たな役割-」
  • Place of Presentation: 東京
  • Year and Date: 2008-05-20
• [Presentation] 孤発性ALS病態関連分子の探索と疾患モデルの開発 (2008)
  • Author(s): 田中章景, et.al.
  • Organizer: 第49回日本神経学会総会、シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] An oral Hsp90 inhibitor ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model (2008)
  • Author(s): Adachi, H., Tokui, K., Waza, M., Katsuno, M., Minamiyama, M., Doi, H., Tanaka, F., Sobue G.
  • Organizer: Neuroscience 2008
  • Place of Presentation: Washington DC, USA
• [Presentation] An oral Hsp 90 inhibitor ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model (2008)
  • Author(s): Adachi H, et.al.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Washington DC, USA
• [Presentation] Skeletal insole involvement in spinal and bulbar muscular atrophy (2008)
  • Author(s): Katsuno M, et.al.
  • Organizer: The 19 th International Symposium on ALS/MND
  • Place of Presentation: Birmingham, UK
• [Presentation] Reversible disruption of retrograde axonal transport in spinal and bulbar muscular atrophy (2006)
  • Author(s): Katsuno, M., Adachi, H., Minamiyama, M., Waza, M., Tokui, K., Jiang, Y.M., Banno, H., Suzuki, K., Tanaka, F., Sobue, G.
  • Organizer: 17th International Symposium on ALS/MND
  • Place of Presentation: Yokohama, Japan
• [Presentation] Gen expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis (2006)
  • Author(s): Tanaka, F., Jiang, Y.M., Yamamoto, M., Huang, Z., Katsuno, M., Adachi, H., Niwa, J.I., Doyu, M., Sobue, G.
  • Organizer: 17th International Symposium on ALS/MND
  • Place of Presentation: Yokohama, Japan
• [Book] Clinical features and Molecular Mechanisms of spinal and bulbar muscular atrophy (SBMA).(Shamim I. Ahmad ed., In Diseases of DNA Repair.) (2009)
  • Author(s): Katsuno, M., Banno, H., Suzuki, K., Adachi, H., Tanaka, F., Sobue, G.
  • Publisher: Landes Bioscience
• [Patent(Industrial Property Rights)] 球脊髄性筋萎縮症治療薬 (2009)
  • Inventor(s): 祖父江元、勝野雅央、南山誠
  • Industrial Property Rights Holder: 未定
  • Filing Date: 2009-12-05
• [Patent(Industrial Property Rights)] 球脊髄性筋萎縮症治療薬 (2009)
  • Inventor(s): 祖父江元、勝野雅央、南山誠
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Number: 2009-277101
  • Filing Date: 2009-12-05